Ozzy Osbourne's Genome Reveals Some Neandertal Lineage

What genetic oddities does rock's Prince of Darkness and beheader of bats have entangled deep in his genetic code? Knome, the company that analyzed Ozzy's full genome, divulges some of the details in a Q&A

The one-time front man for heavy metal band Black Sabbath has joined the likes of DNA co-discoverer James Watson and Harvard University professor Henry Louis Gates on the short roster of people to have their full genome sequenced and analyzed.

Ozzy Osbourne let a little blood to submit to the testing in July. Cofactor Genomics, a Saint Louis–based company, sequenced Osbourne's genome; Knome, Inc., which also helped raise money for the project, analyzed the data.

For his part, Osbourne was at first skeptical about the project, he explained in his October 24 Sunday Times of London column. But the platinum-record artist then began to wonder if he, in fact, might have something to offer science.

"I was curious," he wrote in his column. "Given the swimming pools of booze I've guzzled over the years—not to mention all of the cocaine, morphine, sleeping pills, cough syrup, LSD, Rohypnol…you name it—there's really no plausible medical reason why I should still be alive. Maybe my DNA could say why."

But what can a bunch of genetic code tell us about someone's propensity to become the ordained "Godfather of Heavy Metal" or to bite the head off a live bat on stage?

Scientific American spoke with Jorge Conde, co-founder and chief executive of Cambridge, Mass.–based Knome, and Nathan Pearson, the company's director of research, who had sat down with Ozzy earlier to go over the results of the analysis.

Ozzy and his wife Sharon Osbourne will also relay some of the results—more "Down to Earth" than via "Ozzmosis"—Friday at the TEDMED 2010 meeting in San Diego.

[An edited transcript of the interview follows.]

Why did Ozzy want to have his genome sequenced?
Jorge Conde: The main question for Ozzy was: Is there any information in there that could explain Ozzy?

I think he was curious about how he had managed to survive a pretty hard life in a lot of ways. So there were some questions around that—how substance use had affected him and how he metabolized things. He was also interested in specific health questions—he was diagnosed with a Parkinson's-like condition. He was also very interested in what we could tell him about his ancestry.

Nathan Pearson: He was really curious to know about his Parkinson's-like symptoms, so we looked pretty closely in his genome for that kind of stuff. We found a few hints, but we couldn't tell him why he has symptoms like a tremor. And frankly, his history of drug abuse probably contributed to that, too.

He asked us good questions about dopamine. Many of the variants in his genome are about how the brain processes dopamine.

Is Ozzy the first rock star to have his full genome sequenced?
Conde: Yes, as far as I know. I can definitely tell you he's the first prince of darkness to have his genome sequenced and analyzed.

Can we see in his genome any traces of his legendary rock-and-roll lifestyle—or evidence of his body's efforts to repair any damage?
Conde: We cannot find the "Ozzy Osbourne" gene. But what we did see, as one of our scientists refers to it, is a lot of interesting smoke—but not any specific fire. We found many variants—novel variants—in genes associated with addiction and metabolism that are interesting but not quite definitive.

So can his genomes tell us anything about his ability to survive so many years of hard partying?
Pearson: I talked with Ozzy, and we looked at the genome with an eye toward the nerves. If you think about what makes Ozzy unusual, it's that he's a world-class musician, he has an addictive personality, he has a tremor, he's dyslexic, he gets up very early in the morning. And many of these can be traced back to the nervous system.

One variant involves a gene that makes CLTCL1, which is a really interesting protein. When a cell takes in things from the outside membrane, it pulls itself in like a basket to pull things in. It does this in all kinds of cells, including nerve cells. He has two copies of an unusual variant that makes a grossly different version of the protein than most people produce. Here's a gene that's central to how nerve cells communicate with each other, so it's curious to us to see a grossly different protein variant. It's thought provoking.

We didn't find anything that can explain to you from point A to point B why Ozzy can think up good songs or why he is so addicted to cocaine, but we found some things that would be interesting to follow up on.

Such as?
Pearson: Alcohol dehydrogenase genes. They're involved in breaking down alcohol when you drink. Ozzy has an unusual variant near one of his alcohol dehydrogenase genes, ADH4, that help regulate how much of the protein gets made. Given his troubles with alcohol in the past, obviously we would like to clarify why his body responds differently than other people's.

Did his genome show any predisposition for serious diseases?
Pearson: He's a 61-year-old healthy guy, and that speaks for itself. That suggests he's done okay in the genetic lottery.

It also speaks to how early on we are in this field. Genome-wide association studies are notoriously weak in identifying variants that strongly determine our health. They look at variants that are common in the population. Those are easy to look at, but variants don't get to be common in the population if they're very harmful. It's clear now that you have to look also—and especially—at rare variants. And like everyone, Ozzy carries several hundred thousand variants that have never been seen by scientists. It's going to be a while before we get enough data as a society to understand those variants.

Were there any big surprises hiding in his genome?
Pearson: For a long time we thought that Neandertals didn't have any descendents today, but it turns out that Asians and Europeans have some evidence of Neandertal lineage—like a drop in the bucket. We found a little segment on Ozzy's chromosome 10 that very likely traces back to a Neandertal forebearer.

Ozzy, of course, was tickled to hear this. But Knome founder George Church's genome has about three times as much Neandertal, which we thought was funny.

What has Ozzy's response to the findings been so far?
Pearson: From what I can tell, Ozzy was really very sincerely interested in this. He is really very engaged. As I was leaving Ozzy's home, I was in the atrium—and I think he had thought I had already left for my cab, but I could hear him say to his assistant [in an Osbourne-like accent], "That was really interesting."

What can we learn from Ozzy's genome?
Pearson: I think one lesson is understanding music. It's a pretty interesting thing we do at humans—that some of us can synchronize to a beat, that we like to sing songs. But we don't understand it well genetically, so one of the open questions is we'll get a better understanding of what makes a good musician, what kinds of variants help us keep a beat, make a good tune. I think looking ahead, sequencing the genomes of more musicians would be a good idea.

If you could sequence any other celebrity genomes, whose would you choose?
Pearson: Ozzy suggested Keith Richards. Our partners who did the sequencing suggested we sequence Ozzie Smith, the baseball player, as a control. He's always been a good teetotaler.

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